Human vision starts when photoreceptors collect and respond to light. Normal photoreceptor function and its support from the underlying retinal pigment epithelium (RPE) are essential for normal vision, yet techniques to assess these processes in vivo are limited. Current optical and electrophysiological techniques have limited spatial resolution and sensitivity, and target only specific functional processes. New optical modalities that are rapid, specific, and noninvasive hold the promise of greatly expanding our capability to monitor more accurately and completely the photoreceptor RPE complex. We will use adaptive optics (AO) and optical coherence tomography (OCT) to achieve unprecedented 3D resolution for studying physiological mechanisms at the cellular level in the photoreceptor and RPE layers. Further improvements will be realized using AOOCT in conjunction with an exquisitely sensitive phase technique that we have developed and that measures optical length changes as small as 45nm.This is slightly thicker than a single cone outer segment (OS) disc and nearly 100times better than the axial resolution of ultra high resolution OCT. The specific aims are to: (1) Determine the physical parameters that control light capture in photoreceptors; (2) Evaluate properties of light scatter in photoreceptors; and (3) Evaluate properties of light scatter in RPE. PUBLIC HEALTH RELEVANCE: The long term goal of this research is to establish high-resolution imaging methods that probe structure and function of the retina at the cellular scale. The target cells in this study are photoreceptors and retinal pigment epithelial cells, both associated with the capture of light and the first step in seeing. As disease starts at the cellula and molecular levels, the ability to study these pathological disruptions at the single cell level and in patients promises improvements in early detection and treatment monitoring of some of the most blinding diseases in the world.